Psychiatry Psychiatry and psychopharmacotherapy named after. P.B. Gannushkina – Ixel in clinical practice

The antidepressant Ixel (Milnacipran - international name) is often used for depressive conditions, anxiety disorders and disturbances in the functioning of the nervous system.

The drug normalizes the general condition, improves the psyche and promotes rapid recovery of the body.

The drug is available in the form of capsules with a gelatin structure, the size range of which is No. 4. The capsules have an orange cap with a pink tint, and there is a black imprint “IXEL” on the surface of the capsules. Inside the capsules there is a powdery mixture with a white or almost white color; they are contained in blisters of 14 pieces. Cardboard packages contain 2 or 4 blisters.

Pharmacological actions

The main active ingredient belongs to the pharmacotherapeutic group of third-generation antidepressants intended for the treatment of anxiety disorders and depression. Milnacipran hydrochloride has absolutely no effect on the conductivity or relaxation of the heart.

Also, the main component does not change higher brain functions and has a mild sedative effect. Milnacipran shows increased effectiveness in the treatment of people with sleep problems that are caused by depression.

In such a situation, the total duration of dreams increases, the period of falling asleep is minimized, the interval before the onset of the rapid phase of sleep increases, and the number of night awakenings decreases. The effectiveness of the drug is comparable to the positive effect of tricyclic sedatives.

When taken orally, the active substance is well absorbed. Its bioavailability reaches eighty-five percent and is not determined by characteristics and nutrition.

The maximum level of milnacipran in the blood is recorded approximately two hours after oral administration. When using Ixel in a single dosage of fifty milligrams, the maximum concentration of the active microelement in the blood is approximately one hundred and twenty nanograms per milliliter.

When using the medication in dosages that do not exceed two hundred milligrams, a dose-dependent increase in the maximum level is observed. After repeated courses, equilibrium concentration is achieved within two to three days, and it is seventy to ninety percent higher than when using a single dose.

Differences in the measured value between individuals remain low. The active trace element binds to blood proteins in small quantities (about thirteen percent). The volume of distribution is equal to five liters per kilogram with a total clearance of approximately forty liters per hour. Nonrenal and renal measures of the volume of plasma that is cleared of a drug per unit time are the same.

Release form and composition

Ixel is available in the form of hard gelatin capsules with the main active ingredient milnacipran hydrochloride, its content in capsules is:

• Orange-pink in color, which are stamped in black “25” on the body and IXEL on the cap – 25 mg;
• Yellow-orange in color, on the body of which there is an imprint “50” and the inscription IXEL on the orange-pink cap - 50 mg.

The capsule shell contains titanium dioxide (E171), red and yellow iron oxide (E172), gelatin.

Inside the capsules there is a white powder, the auxiliary components of which are: calcium carmellose, anhydrous colloidal silicon dioxide, calcium hydrogen phosphate dihydrate, povidone K30, talc, magnesium stearate.

Ixel is supplied to the pharmacy chain in blisters of 14 capsules.

What other positive properties does Xcel have?

Milnacipran is not involved in metabolic processes. No active metabolic product was detected; the component combines with glucuronic acid. The half-life of the main microelement "Ixela" is approximately eight hours.

Milnacipran is excreted in urine (approximately ninety percent of the dose taken) as a result of the transport of substances from the blood into the lumen of the tubules. After completion of therapy, the active substance is completely eliminated from the body within two to three days after cessation of treatment. Improper liver function does not provoke significant changes in the parameters of the active substance.

The rate of excretion of the active ingredient decreases in proportion to the degree of kidney damage in people with renal failure. In people of retirement age, the pharmacokinetic parameters of milnacipran do not change much. But when selecting the dosage, it is important to take into account the physiological changes in kidney function in elderly patients.

According to information obtained from preclinical studies, chronic use of Ixel primarily affects the liver. Adverse effects were observed when using high doses, approximately ten times higher than prescribed, and were reversible.

Preclinical studies obtained during reproductive toxicity, genotoxicity, and habitual toxicity studies of milnacipran do not support human health risks. Milnacipran hydrochloride has neither carcinogenic nor mutagenic effects.

Ixel

Description of the dosage form

Description of the dosage form

25 mg capsules:
orange-pink body and cap, consisting of titanium dioxide, red and yellow iron oxide, gelatin.

50 mg capsules:

the lid is orange-pink, the body is rust or reddish-brown, consisting of titanium dioxide, red and yellow iron oxide, gelatin.

Instructions

INSTRUCTIONS for medical use of the drug IXEL (IXEL)

APPROVED

Pharmacological Committee of the Russian Ministry of Health February 24, 2000, protocol No. 3

Description

Capsules 25 mg - body and cap of orange-pink color, consisting of titanium dioxide, red and yellow iron oxide, gelatin.

Capsules 50 mg - orange-pink cap, rust or reddish-brown body, consisting of titanium dioxide, red and yellow iron oxide, gelatin.

Chemical name

(Z)−2-aminomethyl−1 phenyl-N,N-diethylcyclopropanecarboxyamide hydrochloride

Compound.

1 capsule contains milnacipran hydrochloride (active ingredient) 25 or 50 mg and other ingredients: calcium hydrogen phosphate dihydrate 50.925 or 101.85 mg, carmellose calcium 22.15 or 44.3 mg, povidone K 30 (polyvidone K 30) 2.1 or 4.2 mg, anhydrous colloidal silica 0.625 or 1.25 mg, magnesium stearate 2.1 or 4.2 mg and talc 2.1 or 4.2 mg, respectively.

Pharmacological properties

Pharmacodynamics

An activating antidepressant, it is a selective monoamine reuptake inhibitor (serotonin and norepinephrine).

Ixel does not have the ability to bind to m-cholinergic receptors, alpha1-adrenergic receptors or histamine H1 receptors, as well as D1- and D2-dopaminergic, benzodiazepine and opioid receptors. It does not have a sedative effect, but physiologically improves night sleep and does not affect cognitive functions. Ixel does not affect the conduction system of the heart and blood pressure, which is especially important for elderly patients who are constantly taking cardiotropic drugs.

Pharmacokinetics

After oral administration, Ixel is well absorbed. The bioavailability of the drug is about 85% and does not depend on the nature and diet. Cmax in plasma is achieved approximately 2 hours after taking the drug. After repeated doses of the drug, an equilibrium state is achieved within 2–3 days (Cmax = 216 mg/ml). Plasma protein binding is weak (about 13%) and is not accompanied by saturation. The metabolism of Ixel is limited primarily to conjugation with glucuronic acid. There is no active metabolite. T1/2 - 8 hours. Excreted mainly by the kidneys (about 90% of the administered dose). The drug is completely eliminated from the body within 2–3 days.

Indications

Depressive disorders of varying severity.

Directions for use and doses

Ixel is intended for oral use. The average daily dose of the drug in adults is 100 mg. The daily dose should be administered in 2 doses in the first half of the day, preferably with meals. Depending on the severity of symptoms, the dose of the drug can be increased to 250 mg/day. In patients with renal failure (glomerular filtration rate 10–50 ml/min), a reduction in the daily dose is recommended depending on the level of creatinine clearance. The duration of use is determined individually.

Side effect

Side effects of Ixel are observed quite rarely, mainly during the first 2 weeks of treatment, and are insignificantly expressed. Typically, side effects resolve on their own as depressive symptoms regress and do not require cessation of treatment. The most common side effects include anxiety, dizziness, increased sweating, hot flashes, and difficulty urinating. Nausea, vomiting, dry mouth, constipation, tremor, and palpitations are less common. In rare cases, serotonergic syndrome may develop, as well as a moderate increase in transaminase levels without any clinical manifestations. The severity and number of side effects can be reduced by gradually increasing the dose of the drug during treatment.

Contraindications

Absolute contraindications include:

- hypersensitivity to milnacipran;

- age under 15 years (due to lack of clinical data);

- simultaneous administration of non-selective and selective MAO type B inhibitors, as well as sumatriptan.

The drug is not recommended for use:

- simultaneously with adrenaline, norepinephrine, clonidine and its derivatives;

— selective MAO type A inhibitors, digoxin;

- in the presence of urinary tract obstruction (mainly with prostatic hyperplasia);

- during pregnancy and breastfeeding.

special instructions

Ixel can be prescribed no earlier than 14 days after discontinuation of MAO inhibitors. In addition, the period of time from stopping taking Ixel to starting therapy with MAO inhibitors should be at least 7 days.

Ixel should be used with extreme caution in patients with prostate adenoma, with a history of epileptic seizures and in patients with arterial hypertension or cardiopathy (due to a slight increase in heart rate). During the treatment period, it is recommended to avoid drinking alcohol. You should also refrain from potentially hazardous activities that require increased attention and rapid psychomotor reactions.

Drug interactions

Contraindicated combinations:

- with non-selective (iproniazide), selective MAO type B inhibitors (selegiline), as well as sumatriptan due to the risk of developing serotonergic syndrome, arterial hypertension and coronary spasm. The minimum time interval after completion of treatment with the above drugs and the prescription of Ixel is 2 weeks.

Not recommended combinations:

- with adrenaline and norepinephrine due to the risk of arterial hypertension and arrhythmia;

- with clonidine and related compounds due to a decrease in their hypotensive effect;

- with digoxin (especially when administered parenterally) due to the risk of developing tachycardia and arterial hypertension;

- with MAO type A inhibitors (moclobemide, toloxatone) due to the risk of developing serotonergic syndrome.

Overdose

If the dose of Ixel is accidentally increased, one of the first symptoms is nausea, vomiting, sweating and constipation.

With an overdose exceeding 800–1000 mg, vomiting, difficulty breathing and tachycardia occur.

After taking an excessively high dose (1900–2800 mg of milnacipran) in combination with other psychotropic drugs (most often benzodiazepines), drowsiness, hypercapnia and impaired consciousness are added to the symptoms described above.

No manifestations of cardiotoxicity, as well as deaths, were observed with overdoses of Ixel. There is no specific antidote for milnacipran. Treatment involves gastric lavage at the first stage, followed by symptomatic therapy. It is also recommended to monitor the patient's condition for at least 24 hours.

Release form

Capsules of 25 and 50 mg: 28 or 56 pcs per pack.

Storage conditions

In a dry, cool place at a temperature not exceeding 30 °C. Keep out of the reach of children.

Best before date

3 years.

Conditions for dispensing from pharmacies

By doctor's prescription.

Manufacturer

Pierre Fabre Medicament Production

A comment

Marketing in the Russian Federation is carried out by Janssen Pharmaceutica NV

Composition and release form

Composition and release form

14 pcs in blister; There are 2 or 4 blisters in a box.

14 pcs in blister; There are 2 or 4 blisters in a box.

Pharmacological properties

pharmachologic effect

Inhibits the reuptake of norepinephrine and serotonin.

Pharmacokinetics

Well absorbed from the gastrointestinal tract. Bioavailability - about 85%. Cmax is reached after approximately 2 hours. Plasma protein binding is about 13%. Metabolized mainly by conjugation with glucuronic acid. T1/2 - 8 hours. Excreted mainly by the kidneys (about 90%).

Indications

Indications

Depressive disorders of varying severity.

Contraindications

Contraindications

Hypersensitivity, prostatic hyperplasia, simultaneous use of MAO inhibitors type A and B, selective serotonin reuptake inhibitors, adrenaline, norepinephrine, clonidine, digoxin, moclobemide, toloxatone; pregnancy, breastfeeding, age up to 15 years.

Directions for use and doses

Directions for use and doses

Inside

(preferably with meals), 50 mg 2 times a day. The duration of use of the drug is determined individually.

Use during pregnancy and breastfeeding

Contraindicated. Breastfeeding should be stopped during treatment.

Interaction

Incompatible with MAO inhibitors and serotonergic drugs (such as tryptophan or fenfluramine). Changes the level of lithium in the blood.

Overdose

Unlikely. There are no specific antidotes. Treatment is symptomatic.

Precautionary measures

It is prescribed with extreme caution to patients with prostate adenoma, a history of epileptic seizures, arterial hypertension, and cardiomyopathy. A two-week interval is required between taking MAO inhibitors and Ixel. In patients with renal failure, a dose reduction is recommended depending on creatinine Cl. Alcohol consumption is not allowed. Should not be used during work by vehicle drivers and people whose profession involves increased concentration of attention.

Side effects

Side effects

Dizziness, anxiety, increased sweating, hot flashes, palpitations, tremors, difficulty urinating, dry mouth, nausea, vomiting, constipation.

Indications and contraindications for the medication

The use of the drug "Ixel" is recommended for the treatment of depression of varying degrees of severity. The drug has certain prohibitions, for example:

1. Combined use with Sumatriptan, as well as non-selective and selective inhibitors of monoamine oxidase type B.
2. Age up to fifteen years.
3. A pathological condition in which the outflow of urine is disrupted.
4. Pregnancy period.
5. Lactation (the process of formation, accumulation and periodic excretion of milk in a woman).
6. Excessive sensitivity to trace elements of the drug.

Contraindications

Contraindications:

Hypersensitivity, benign prostatic hyperplasia, simultaneous use of MAO inhibitors type A and B, selective inhibitors of neuronal reuptake of serotonin, adrenaline, norepinephrine, clonidine, digoxin, moclobemide, pregnancy, breastfeeding, children and adolescence (up to 15 years). Use during pregnancy and breastfeeding: Contraindicated during pregnancy. Breastfeeding should be stopped during treatment.

In what cases should you be careful when taking the drug?

It is necessary to be especially careful when using Ixel for people suffering from the following conditions and diseases:

1. Angle-closure glaucoma (a defect that develops due to increased intraocular pressure).
2. Epilepsy (a chronic neurological disease that manifests itself in the body’s predisposition to the sudden appearance of convulsive attacks).
3. Kidney failure.
4. Arterial hypertension (persistent increase in blood pressure from one hundred and forty to ninety millimeters of mercury and higher).
5. Cardiomyopathy (damage to the heart muscle that is not associated with inflammatory, tumor, ischemic etiology, the manifestations of which are cardiomegaly, as well as heart failure and arrhythmias).

Instructions for use of "Ixela"

The tablets must be taken orally, in the morning, preferably during breakfast. The dosage and duration of treatment are determined by the attending physician based on the individual severity of symptoms.

The recommended average daily dosage of Ixel is one hundred milligrams, which should be divided into two doses. To achieve a stable pharmacological effect in severe cases of the disease, it is allowed to increase the content of the active substance, but not more than two hundred and fifty milligrams per day. For patients suffering from renal failure, the daily dosage should be reduced.

Side effects

In their reviews, patients who took the drug “Ixel” talk about a number of negative effects when used incorrectly and dosing, for example:

1. Dizziness.
2. Sense of anxiety.
3. Migraine (a neurological disease, the most common and characteristic symptom of which is episodic or regular severe and painful attacks of headache in one side of the head).
4. Tremors (sharp, rhythmic movements of the legs, arms or torso, which are provoked by muscle spasms).

According to reviews, “Ixel” causes side effects from the stomach and intestines:

1. Dry mouth.
2. Intestinal obstruction (difficulty or insufficient emptying).
3. Vomiting.
4. Increased sweating.
5. Skin rashes.

Symptoms of drug overdose

In case of Ixel poisoning, the first signs of this condition are constipation, excessive sweating, nausea, and vomiting. The use of the drug in a dosage of more than a thousand milligrams provokes the appearance of tachycardia and breathing problems.

According to reviews of Ixel, the antidepressant, when used in extremely high concentrations (two thousand eight hundred milligrams) together with other psychotropic drugs, causes disturbances of consciousness, hypercapnia (increased levels of carbon dioxide in the blood, poisoning caused by carbon dioxide).

Poisoning with milnacipran hydrochloride does not result in cardiac toxicity. In this case, it is necessary to rinse the stomach, use activated carbon and contact a medical specialist who will prescribe comprehensive treatment. There is no specific antidote to Ixel. In this case, the general condition of the patient should be monitored throughout the day.

Possible side effects of Ixel and overdose

Undesirable consequences from taking the drug can be observed in almost all organs and systems. Below we list the adverse reactions from different organs and systems:

1. Mental health – agitation, anxiety, worsening depression, bulimia, anorexia, sleep disorders, suicidal thoughts, panic attacks, loss of consciousness and others.
2. Nervous system – headaches, tremors, dizziness, sensory disturbances, drowsiness, restlessness, fainting, etc.
3. Gastrointestinal tract - nausea, vomiting, change in stool consistency, xerostomia, abdominal pain.
4. Skin – rashes, itching, increased sweating, urticaria, dermatitis and other reactions.
5. Musculoskeletal system – pain in muscles and bones, muscle rigidity.
6. Urinary system – urinary disorders, enuresis.
7. Reproductive system – ejaculation disorder, erectile dysfunction, amenorrhea, hypermenorrhea.
8. Cardiovascular system - increased heart rate, disturbances in heart rhythm, excitability and conduction, hypertension, hypotension, Raynaud's disease.

Hemorrhages in the mucous membranes and skin, allergies, hyperlipidemia, cough, dry nose, weakness, and increased body temperature may also be observed.

An overdose occurs after consuming 800 - 1000 milligrams of the drug. It manifests itself as vomiting, difficulty breathing, and increased heart rate. Taking a dose of 1900–2800 mg while taking other psychotropic drugs may worsen the condition even further. To the already listed symptoms, drowsiness is added, the respiratory center is depressed and the carbon dioxide content in the blood increases, which leads to loss of consciousness. Ixel does not have a specific antidote, so if it is poisoned, standard care is provided, which includes:

• gastric lavage;
• intake of adsorbents;
• symptomatic therapy.

After stabilization of the condition, it is recommended to monitor the patient for another day in order not to miss delayed effects.

See also:

What are Amlorus tablets for and instructions for the drug?

Features of Ixela

Due to a slight increase in heart rate during the use of the drug, it is important for patients with cardiomyopathy and arterial hypertension to take the medication with extreme caution.

The occurrence of negative effects, as a rule, is extremely rare and does not require discontinuation of the drug. Reactions appear during the first fourteen days of therapy, are mild, and disappear on their own as the signs of depressive disorder subside.

To reduce the severity and number of adverse reactions, it is recommended to increase the dosage gradually during treatment.

Possible side effects:

Before buying Ixel (Milnacipran), patients should be aware of possible adverse reactions to the active substance. It is worth saying that the drug we are considering is positively perceived by the body, especially in the first two weeks of therapy. If there are any adverse reactions, they manifest themselves with a weakly expressed effect and stop on their own, without requiring treatment. The most common reactions are:

• Feeling of anxiety.
• Hyperhidrosis.
• Problems with urination.
• Severe dizziness.
• Nausea, vomiting.
• Constipation, gastrointestinal problems.
• Increased heart rate.
• Serotonin intoxication may develop.

The severity of side symptoms can be reduced by gradually increasing the dose of medication during therapy.

Adviсe

The medication can be used after stopping the use of monoamine oxidase inhibitors no earlier than two weeks, and the use of MAO inhibitors must be started seven days after discontinuation of the drug. It is prohibited to drink alcohol during treatment.

Doctors in reviews of Ixel indicate that when using the drug, you must refrain from driving a car or using complex machinery throughout the entire course.

Can Ixel be used during pregnancy?

Since there is no information regarding the safety and effectiveness of using the active substance in pregnant women, it is not recommended to use Ixel during pregnancy.

The active trace element passes into breast milk, so the drug should not be taken during lactation. In case of malfunction of the kidneys, the medication should not be prescribed with concomitant obstruction of the genitourinary system. Patients with renal failure should use the drug with caution. This may require a dosage reduction, which is associated with an increase in the half-life of milnacipran.

According to the instructions for use and patient reviews of Ixel, it is known that it is prescribed with extreme caution to patients with cirrhosis of the liver (a pathological process in the liver, which is considered the result of impaired microcirculation in the system of hepatic vessels and bile ducts).

special instructions

The drug should be used with caution in case of angle-closure glaucoma and epilepsy.

The drug should be used with extreme caution in patients with adenoma (benign hyperplasia) of the prostate gland, with a history of seizures, arterial hypertension, cardiomyopathy (due to a slight increase in heart rate).

In patients with renal failure (creatinine clearance 50-10 ml/min), a reduction in the daily dose is recommended depending on the clearance values.

Milnacipran can be prescribed no earlier than 14 days after discontinuation of MAO inhibitors. In addition, at least 7 days must pass from the moment of discontinuation of milnacipran to the start of therapy with MAO inhibitors.

During the treatment period, avoid drinking alcohol.

Impact on the ability to drive vehicles and operate machinery

During the treatment period, patients should refrain from engaging in potentially hazardous activities that require increased attention and rapid psychomotor reactions.

Drug interactions

When combined with Norepinephrine and Adrenaline, arterial hypertension and arrhythmia may occur. If local anesthesia is necessary when using a sedative, the dosage should not be higher than 0.1 milligrams per ten minutes or 0.3 milligrams per hour.

The drug should not be prescribed together with Digoxin, as this can provoke the appearance of arterial hypertension and tachycardia.

It is not recommended to use the drug with Clonidine and other similar compounds due to a decrease in their hypotensive effect.

Overdose

With a slight increase in dose, sweating, constipation, vomiting and nausea may occur. Taking the drug in a dosage exceeding 800-1000 mg causes difficulty breathing, vomiting and tachycardia. An excessively high dosage of the drug (1900-2800 mg) in combination with other psychotropic drugs can add hypercapnia, increased drowsiness, and impaired consciousness to the symptoms described above.

In cases of overdose, gastric lavage and symptomatic therapy should be performed.

Reviews about "Ixel"

Patients who have taken this medicine leave positive feedback. They confirm that the drug is excellent for treating prolonged depressive disorders and panic attacks. As a result, interest in life appears again, anxiety and feelings of weakness disappear, and almost no side effects are observed.

It must be used for a long time (from six months or longer), gradually reducing the dosage. But some patients, in their reviews of the drug Ixel, talk about the high cost of the medicine and the need to buy it to order. And also in rare situations, poor effectiveness of the drug and manifestations of allergies are noted. The price for Ixel varies from 1,200 to 3,000 rubles depending on the region and pharmacy chain.